Role of heat shock proteins in renal function and adaptation to heat stress: Implications for global warming

Table 1 Effect of heat stress on renal function in high-risk populations: Clinical, investigation, manifestations, and prognostic implications

High-risk populations	Systemic clinical manifestations	Organ-specific clinical manifestations	Investigation	Prognosis	Ref.
Outdoor workers	Fever, dizziness, dehydration, fatigue, and hypotension	Flank pain, reduced urine output, and peripheral edema (renal and cardiovascular systems)	Elevated creatinine and BUN levels, decreased eGFR, and proteinuria	High risk of AKI and CKD, and recurrent hospitalizations	Chapman et al[163], Gallo-Ruiz et al[170]
Agricultural laborers	Fatigue, intense thirst, and heat exhaustion	Flank pain and oliguria (renal system)	Electrolyte disturbances, elevated creatinine levels, and proteinuria	High risk of nondiabetic CKD; repeated AKI episodes due to chronic dehydration	Wesseling et al[178], Nerbass et al[179]
Kitchen workers (chefs)	Dehydration, fatigue, and dizziness	Oliguria and lower limb edema (renal system)	Reduced eGFR and proteinuria	2.8-fold increased risk of AKI compared with the general population	Koh[171]
Brick manufacturing workers	Heat exhaustion, fatigue, and muscle pain	Flank pain and oliguria (renal system)	Elevated BUN and creatinine levels and reduced eGFR	High probability of latent CKD due to prolonged heat exposure	Gallo-Ruiz et al[170]
Marathon runners	Dehydration, muscle cramps, and heat exhaustion	Flank discomfort and urgency of urination (renal system)	Electrolyte imbalance and elevated creatinine levels	Transient AKI; reversible with prompt management	Tidmas et al[172]
Elderly individuals (aged ≥ 65 years)	Impaired thirst sensation, dizziness, and altered mental status	Hypertension, cardiac insufficiency, and oliguria (cardiovascular and renal systems)	Reduced creatinine clearance, elevated N-terminal pro B-type natriuretic peptide levels, and electrolyte imbalance	Rapid CKD progression; higher risk of hospitalization and mortality	Glaser et al[173], Johnson et al[174], Tran et al[175]
Pregnant women	Fatigue, hypotension, and dizziness	Proteinuria, pedal edema, and gestational hypertension (renal and cardiovascular systems)	Decreased eGFR, elevated liver enzyme levels, and proteinuria	Increased risk of preeclampsia, intrauterine growth restriction, and pregnancy-related AKI	Moronge et al[176]
Immunocompromised individuals	Persistent fever, fatigue, and increased infection susceptibility	Recurrent urinary tract infections and hematuria (renal system)	Elevated C-reactive protein levels, leukopenia, and increased creatinine levels	High risk of renal deterioration; susceptibility to multiorgan failure	Leon et al[177]

AKI: Acute kidney injury; BUN: Blood urea nitrogen; CKD: Chronic kidney disease; eGFR: Estimated glomerular filtration rate.

Table 2 Summary of representative studies on heat stress and kidney injury

Ref.	Study design and population characteristics	Primary methods for heat stress assessment	Primary methods for kidney injury/health assessment	Key findings related to kidney injury/health
Koh[171], 2024	A cross-sectional descriptive study was conducted among kitchen workers in Kampar, Malaysia	WBGT, thermal work limit, ambient temperature, humidity, questionnaire, workload observation	Urinalysis dipstick (10 parameters: Leukocytes, nitrites, glucose, potential of hydrogen, protein, ketones, specific gravity, blood, bilirubin, and urobilinogen) preshift and postshift; self-reported kidney-related symptoms	In a study conducted across 14 kitchen settings in Kampar, WBGT was recorded at 27.2 ± 1.0 °C, exceeding the recommended action level of 25 °C. These findings classify kitchen workers as being at a medium risk of heat stress. A total of 38.7% of kitchen workers reported symptoms of heat-related illness, with excessive sweating (45.1%), thirst (25.8%), and fatigue (24.2%) being the most commonly reported symptoms. Prolonged exposure to such heat stress conditions may increase the risk of dehydration-related kidney injury, particularly among workers with inadequate fluid intake or preexisting health conditions
Venugopal et al[180], 2016	A cross-sectional descriptive study was conducted among 442 workers across 18 organized and unorganized workplaces in India	WBGT measurements, work intensity judgment by an industrial hygienist, HOTHAPS questionnaire on perceived heat exposure, and coping	Self-reported heat-related health effects via the HOTHAPS questionnaire, including urogenital symptoms	A comprehensive evaluation of 18 Indian workplaces, spanning both organized and unorganized sectors, found that most workers were exposed to heat levels exceeding the recommended WBGT thresholds. Those engaged in physically demanding outdoor tasks reported more heat-related health issues, including skin rashes, dehydration, heat syncope, and urogenital discomfort. Statistical analysis revealed considerable associations between workload intensity and adverse health outcomes (χ² = 23.67, P ≤ 0.001), as well as between heat exposure and decreased productivity (χ² = 15.82, P ≤ 0.001). Heat-induced fatigue, illness-related absenteeism, and income loss were major concerns, particularly in the unorganized sector. The findings emphasize the persistent threat of occupational heat stress year-round
Chapman et al[7], 2020	A quasi-randomized crossover experimental trial was conducted involving 13 healthy adult participants	Controlled laboratory exercise (2 hours) in heat (39.7 °C, 32% relative humidity) under 4 conditions (control, water, cooling, and water + cooling); core temperature, skin temperature, body weight loss	Urinary AKI biomarkers (albumin, NGAL, IGFBP7, and TIMP-2) pre-exercise, post-exercise, 1-hour post-exercise, and 24-hour post-exercise	This study is the first to report the distinct urinary biomarker responses of IGFBP7 and TIMP-2 following physical exertion under heat stress conditions. These findings indicate site-specific kidney injury, probably affecting the proximal tubules, where IGFBP7 is predominantly secreted. Occupational heat stress, particularly when accompanied by hyperthermia and dehydration, was found to remarkably elevate AKI biomarkers such as urinary albumin, NGAL, and IGFBP7 in the absence of thermoregulatory interventions such as hydration and cooling
Johnson et al[181], 2019	This review examines the current literature on the effect of increasing global temperatures on kidney health, focusing on heat-related acute kidney disease and CKD, nephrolithiasis, and Urinary tract infections. Data were drawn from studies involving vulnerable populations such as outdoor workers and elderly individuals, particularly in tropical and low-resource settings	Environmental monitoring (e.g., WBGT), heat stress indices (such as predicted heat strain and humidex), and physiological monitoring of workers (e.g., core temperature, heart rate, and dehydration levels)	Monitoring serum creatinine levels and estimated glomerular filtration rate; performing urinalysis to detect proteinuria, hematuria, or crystalluria; and measuring urinary biomarkers such as leukocytes or indicators of tubular injury, electrolyte sodium, and potassium	Global temperature rise and renal implications: The global rise in temperature has led to more frequent extreme heat events, increasing health risks. The kidneys are vital for thermoregulation and fluid-electrolyte balance. However, they are highly vulnerable to damage from heat-related stress. Heat-induced AKI: High ambient temperatures can increase the core body temperature, cause dehydration, and increase plasma osmolality. Both clinical and subclinical heatstroke contribute to AKI through rhabdomyolysis, inflammation, and renal hypoperfusion. CKD linked to heat stress: Repeated heat exposure and dehydration can cause progressive tubular damage, resulting in CKD. This may account for the increasing CKD rates in hot regions, especially among laborers with poor access to cooling and hydration
Glaser et al[173], 2016	This review provides a global perspective with particular emphasis on rural agricultural communities residing in hot-climate regions	Review of existing literature; analysis of temperature trends in CKD epidemic regions	Discussion of CKD of nontraditional origin epidemics; proposed pathophysiology of heat stress nephropathy	A novel form of CKD, unrelated to traditional causes such as diabetes and hypertension, has been increasingly identified among populations exposed to repeated occupational heat stress and inadequate hydration. This condition, often referred to as CKD of nontraditional origin, has shown geographic clustering in hot, rural regions such as Central America, South Asia, and parts of Africa, primarily affecting manual laborers with limited access to rest, shade, and clean water. Climate change is believed to exacerbate the problem through rising temperatures and more frequent extreme heat events, along with reduced water availability

AKI: Acute kidney injury; CKD: Chronic kidney disease; HOTHAPS: High Occupational Temperature Health and Productivity Suppression; IGFBP7: Insulin-like growth factor-binding protein 7; NGAL: Neutrophil gelatinase-associated lipocalin; TIMP-2: Tissue inhibitor of metalloproteinases-2; WBGT: Wet-bulb globe temperature.